At normal conditions there is a substantial water gradient over the skin as it separates the water-rich inside
of the body from the dry outside. This leads to a variation in the degree of hydration from the inside to the
outside of skin and changes in this gradient may affect its structure and function. In this study we raise the
question: How do changes in the water gradient across skin affect its permeability? We approach this
problem in novel diffusion experiments that permit strict control of the gradient in the chemical potential of
water and hence well-defined boundary conditions. The results demonstrate that a water gradient can be
used to regulate transport of drugs with different lipophilic characteristics across the skin barrier. It is shown
that the transport of metronidazole (log Po/w=0.0) and methyl salicylate (log Po/w=2.5) across skin
increases abruptly at low water gradients, corresponding to high degrees of skin hydration, and that this
effect is reversible. This phenomenon is highly relevant to drug delivery applications due to its potential of
temporarily open the skin barrier for transdermal drug delivery and subsequently close the barrier after
treatment. Further, the results contribute to the understanding of the occlusion effect and indicate the
boundary conditions of the water gradient needed to make use of this effect